1. Field of the Invention
The field of the present invention is bone repair and replacement. More specifically, the invention relates to nanocrystalline calcium phosphate powders useful as bone substitute materials and methods of their manufacture.
2. Description of the Related Art
Naturally-occurring bone mineral is made of nanometer-sized, poorly-crystalline apatitic calcium phosphate with a Ca/P ratio between 1.45 and 1.75. See, Besic et al. J. Dental Res. 48(1):131 (1969). These properties impart solubility to bone tissue that allows it to be repaired continually by osteoclasts and osteoblasts. Natural bone grafts are incorporated into a patient's bone through this continual remodeling process in vivo. However, natural bone grafts are associated with problems such as limited availability and painful, risky harvesting procedures for a patient's own autogenous bone, and risks of viral transmission and immune reaction for allograft bone from a cadaver.
Synthetic bone graft materials have been used to avoid the problems associated with natural bone grafts. Desirable properties for synthetic bone graft materials include biocompatibility with natural bone; structural integrity, so that the graft remains in place and intact until bone heals around it; resorbability, so that the graft material is replaced by bone and is accessible to osteoclasts, osteoblasts, and other bone-forming cells; and compatibility with low-temperature processing, which is desired for incorporating heat-sensitive bone growth proteins or other growth factors.
Bioceramics have been used as bone graft substitute materials. Most commonly used have been calcium phosphate ceramics, such as hydroxyapatite and tricalcium phosphate. Highly crystalline hydroxyapatite is dense, and therefore strong. Such crystalline hydroxyapatite is essentially non-resorbable in vivo, and thus is not replaced by natural bone. Hydroxyapatite solids of lower crystallinity have been reported that are resorbable and chemically similar to the mineral component of natural bone. However, these materials are not strong enough for load bearing applications or other applications requiring high-strength materials. Similarly, tricalcium phosphate materials generally are degraded rapidly in vivo, but lack sufficient strength for weight-bearing applications. Combinations of hydroxyapatite and tricalcium phosphate have been reported, which attempt to mitigate the shortcomings of the individual calcium phosphate components.
Recent developments in bone graft substitute materials include the use of amorphous calcium phosphates. Compositions for use in skeletal repair including an amorphous calcium phosphate and a crosslinkable organic polymer have been reported. Amorphous calcium phosphates have also been combined with more crystalline calcium phosphates to form self-setting ceramic cements. In these cases, preparation of amorphous calcium phosphate is accomplished by low temperature double decomposition between calcium and phosphate ion sources, typically under basic conditions.
New sources for low crystallinity or amorphous calcium phosphate powders for use as bone substitute materials are needed. In particular, nanocrystalline calcium phosphate materials useful in the preparation of high strength calcium phosphate articles are desired.
The preparation of metal alloys by intensive grinding (or milling) of a mixture of metal powders, also called mechanical alloying or mechanical grinding, is a well-known technique. Ball mills and attritors are used to produce fine powders. Ball milling also is used to promote solid state reactions, which result in synthesis of new alloys from elemental powders, or to alter the alloy structure.
When mechanical alloying is used to produce new materials, there is a combination of repeated welding, fracturing and rewelding of the mixture of powder particles mixtures, thereby providing powders of a fine microstructure and facilitating rapid interdiffusion between the particles. Mechanical alloying has been used to form finely divided metal alloys and to promote the formation of intermetallic compounds. High energy milling has even been reported for ceramic materials, for example, to induce chemical reactions between the component ceramic powders and thereby synthesize fine particle-size reacted product.